Approach to administering ocular medication

ABSTRACT

The invention is a device and a method for delivering a dose of a pharmaceutical agent to the eye. The device and method provide a safe and effective way to instill a specified dose of the agent to the eye virtually independent of gravity and posture. The device includes a filter matrix in which the fluid capture and release properties can be modified. The filter matrix is attached to a flexible handle with an impermeable or semipermeable membrane there between.

BACKGROUND

This invention relates to a process and a device for adding a controlleddose of fluid to the eye. Conventional eye drops are difficult to useeven for experienced patients. They are more problematic for children,the elderly, patients with impaired motor skills, and caregivers.Patients risk improper dosing, contamination of the eye droppercontainer, expensive waste due to spillage, and injury to the eyes fromcontact with the dropper bottle. These factors contribute to poorcompliance. In addition, preservatives are added to the drops to providemedicine stability and reduce microbial contamination. Thesepreservatives are known to cause morphological changes to the cornea,conjunctiva, and surrounding areas, which lead to irritation, stinging,burning, epiphora, hyperemia, keratitis, allergic and immune response,and scarring (1).

Subsequent reflex tearing leads to dilution of the medication, which canfurther alter pharmacodynamics. The quantity and concentration of thedrug from conventional eye drops must be increased in order to accountfor the decreased bioavailability due to reflex tearing and thebiophysiologic dynamics of the eye's structure. At least 80% of the dropis lost from excess tearing, spillage due to overflow from the eye's culde sac, and rapid drainage through the nasolacrimal duct which increasesthe risk of systemic side effects (2). The eye has a tear turnover rateof 16% per minute which doubles after using conventional eye drops (3).In order to reach the aqueous humor at measurable levels, highconcentrations of a drug are needed for one drop to be effective sinceonly 3% of conventional eye drops penetrate the cornea (4).

New delivery systems include solutions, suspensions, sprays, gels,inserts, emulsions, mucoadhesives, collagen shields, and contact lenses.These are in addition to devices designed to facilitate the instillationof a drop to the eye. Although these methods are relatively safe, theyhave not fully addressed the main problems associated with dropdelivery. In addition, they have not been implemented on a large scale(5).

What is needed is a new method and device that overcomes the basicchallenges of the current eye dropper system which are:

1. Gravity.

2. Reduced bioavailability due to reflex tearing, eye drop spillover,and eye drop splash-back.

3. Difficult physical manipulation of the eye dropper bottle system bypatients and caregivers.

4. Psychological apprehension of the eye drop instillation process.

5. Eye drop preservation process.

SUMMARY OF THE INVENTION

The subject invention provides a new method for applying a controlleddose of most any ophthalmic agent to the eye without an eyedropper. Thedevice of the present invention comprises a filter matrix attached to anelongated flexible handle separated by a barrier membrane. With thepresent invention, the medication is impregnated within the filtermatrix of the filter matrix applicator (FMA) through various methods andready for activation at a later desired date.

The applicator facilitates the easy instillation of a fully medicateddose of controlled, precise concentration to provide an expectedpharmaceutical effect.

Each medicated applicator can contain a single dose of medication withinthe filter matrix as intended for its own pharmaceutical intent. Themedication would be impregnated into the sterile filter matrix, whichcan be designed with modifiable levels of absorption and saturationaccording to the pharmacodynamics or chemical properties of the drugbeing delivered. The length, width, and depth of the filter matrix alongwith the type of interwoven material determine the absorption andsaturation level of the filter matrix.

The device and method of the present system is designed to provide anoptimal ocular drug delivery, which increases compliance by patients andeffectiveness of delivery of the pharmaceutical agent. The presentinvention further achieves the following objectives:

-   -   Objective 1: Making instillation easy, fast, and comfortable for        the patient, clinician, or caregiver.    -   Objective 2: Increasing bioavailability and optimizing contact        time while maintaining or improving effective dosing.    -   Objective 3: Decreasing or eliminating the use of preservatives        while maintaining pH balance; thereby reducing side effects.    -   Objective 4: Decreasing the dilution and drainage caused by        excess tearing, spillage, and splash-back.    -   Objective 5: Decreasing the risk of contamination and injury to        the eye by eliminating the dropper bottle modality.    -   Objective 6: Improving handling and transport (6).

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 illustrates a top perspective view of an embodiment of the filtermatrix applicator (FMA).

FIG. 1A illustrates a cut away view of an embodiment of the filtermatrix.

FIG. 2 illustrates the front perspective view of an embodiment of theFMA.

FIG. 3 illustrates an alternative disc form embodiment of the FMA beforethe treated disk is installed.

FIG. 3A illustrates a cutaway view of the treated disk of thealternative embodiment of the FMA.

FIG. 4 illustrates the bonded disk in the alternative disc formembodiment of the FMA.

FIG. 5 illustrates an alternative embodiment of the FMA with anun-bonded solid-state carrier.

FIG. 5A illustrates a view of the solid-state carrier for the FMA.

FIG. 6 illustrates the solid-state carrier bonded to form the FMA.

FIG. 7 illustrates the FMA inside a protective sleeve.

FIG. 7A illustrates an un-medicated FMA used as an applicator forophthalmic agents from an eye dropper bottle

FIG. 8 illustrates the FMA with a handle which behaves as both thebarrier membrane and the handle.

FIG. 9 illustrates the administration of an ophthalmic agent using theFMA by pulling down the lower lid and applying to the conjunctiva.

FIG. 10 illustrates the experiment using a mydriatic treated FMA todemonstrate dilation.

FIG. 11 illustrates the experiment using an antimuscurinic treated FMAto demonstrate the effect upon accommodation.

FIG. 12 illustrates the experiment using an ocular hypotensive treatedFMA to demonstrate the efficacy in lowering intraocular pressure ascompared to a standard ocular hypotensive eye drop.

FIG. 13 illustrates the experiment using an olopatadine treated FMA totreat ocular allergy.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Referring to FIGS. 1, 1A, and 2, the present invention comprises adevice, a filter matrix applicator (FMA) (10) comprising a flexibleelongated handle (15) bonded to a sterile filter matrix (20), which canbe medicated or un-medicated, separated by a barrier membrane (30).Flexible elongated handle (15) of a length of approximately but notlimited to 2 inches, with a thickness of at least 0.004 inches. It canbe made of paper, plastic or another suitable flexible material. Thewidth of the handle can be 0.25 of an inch.

The barrier membrane (30, 90) can be made of a semi-permeable orimpermeable material such as rubber, plastic, waxes, petroleum baseproduct, or another material that is waterproof. As shown in FIG. 7A,once the medicated fluid is placed upon the filter matrix (80), thebarrier membrane (90) traps the fluid within the structure of the filtermatrix (80) thereby providing a more exact dose of ophthalmic agent tobe instilled to the eye. If a pre-medicated FMA (10,32) is used, asshown in FIGS. 1,2,3, and 4, saline which is a non-irritant solutioninstead of a medicated fluid (95) is applied to the FMA prior toinstillation to the eye as shown in FIG. 9. With the present inventionany non-irritant eye solution can be use.

In one embodiment, as shown in FIGS. 1 and 1A, the barrier membrane (30)extends the width of the top end of elongated handle (15) and forms abarrier thereto. In an alternative embodiment in FIG. 3, the filtermatrix (40) is in the form of a disc and the barrier membrane (52) formsthe base at one end of handle (35). As depicted in FIGS. 3 and 3A,filter matrix (40) is bonded to base (52) of handle (35) to form FMA(32).

Referring to FIG. 8, there is shown an alternative embodiment of FMA(100) wherein the handle (105) forms the barrier membrane. Inalternative embodiment illustrated in FIG. 8, the barrier membraneserves as both the handle (105) and the waterproof impermeable orsemi-permeable membrane. In this embodiment barrier membrane extends thefull length and width of the handle (105) and bonds to the filter matrix(110).

As shown in FIGS. 1, 2, and 3, the filter matrix (20, 40) is separatedfrom the handle by a semi-impermeable or impermeable waterproofbarrier-membrane (30,52) provides the mechanism wherein the FMA (10)facilitates the efficient and effective entrapment and release ofmedication into solution for the end-user. In use, the barrier membrane(30, 52) optimizes the amount of medication captured within the FMA(10,32) and precipitated into the resultant drop that is instilled tothe eye. The system and device (10) of the present invention reduces theamount of medication that is absorbed or lost in the elongated handle inthe prior art without a barrier membrane.

In the present invention, as depicted in FIGS. 1, 2, 3 and 3A, thefilter matrix (20, 40) can comprise a plurality of strands or fibersinterwoven to create a size that can vary to optimize the capture andrelease of the ocular agent being used. Interwoven fibers (20, 40) formthe matrix to capture the granules of the medicated ocular agenttherein. The size of the filter matrix (20) can be ⅜ inches in depth tofacilitate a surface area for saturation of the ocular agent within thematrix. The perimeter of the filter matrix (20) in FIG. 1 can be a totalof 1 inch. Alternatively the diameter of the filter matrix (40) in FIG.3 can be 0.25 of an inch in diameter.

However, the shape of the filter matrix (20, 40) can vary in size andshape to aid in efficient instillation of the ocular agent to the eye.In the illustrated embodiment in FIG. 1, the filter matrix (20) depictsa polygonal shape and in FIG. 3, the filter matrix (40) is depictedhaving a circular shape. However, the shape of the filter matrix (20,40) is not limited to either shape; instead the shape can vary tooptimize the capture and release of the ocular agent. The filter matrix(40) depicted in FIGS. 3 and 1 can be circular, oval, elliptical, orpolygonal.

In the present invention, each medicated FMA (10) depicted in FIG. 1 cancontain one prescribed medicated dose for a patient. The medicationwould be impregnated within the FMA (10) in a sterile environment. Thefiber can be of various materials with variable levels of absorption andsaturation. In use, the more water repellant the strands the lower thesaturation level of the filter matrix and the more water absorbent thestrands the higher the saturation level of the filter matrix. Thestrands of the filter matrix can be absorbent such as cotton or lessabsorbent such as plastic. In the present invention, the strands of theFMA can be made of cotton, rayon, silk, nylon, various plastic fibers,synthetic fibers and/or any other suitable material. The filter matrixcan be made of a blend of fibers to adjust the capture and releaseproperties of the FMA (10).

In FIGS. 1 and 3, the semi-flexible handle (15, 35), which is separatedfrom the filter matrix (20, 40) by the impermeable membrane (30, 50)allows for easy placement of the fluid to the eye. The handle can beconstructed in various shapes and sizes and of various materials to aidin easy instillation of an ophthalmic agent and to further facilitateproper drop formation to be applied to the matrix.

In an alternative embodiment illustrated in FIGS. 5 and 5A, the volumeof the medication is stabilized within an inert semi-permeable carrier(55) made of materials similar to, but not limited to polyvinylmethylcellulose, loosely bound in place to the elongated handle (60) byan inert viscous carrier such as mineral oil or petrolatum or similarcompounds (55). The solid-state filter matrix (65) shape can be flat orcolumnar. The filter matrix (65) size is based on the nature andquantity of active ingredient of the medication. This embodiment reducesthe need for a drop to be stabilized on the FMA (62) and also allows fortime—release of an ophthalmic compound.

An additional embodiment of the FMA is un-medicated (70), as shown inFIG. 7. In this embodiment, the FMA can be used by placing one drop ofocular medication from an eye dropper bottle onto the FMA and applyingdirectly to the eye in the fashion described in FIG. 9. Therefore,medications not available in a prepackaged FMA form can be administeredwith the advantages of this new technology.

Creation of the FMA

Once the FMA (10, 32) is manufactured as shown in FIGS. 1, 2, and 3, thefilter matrix (20, 40) can be either non-medicated or pharmaceuticallyimpregnated under aseptic conditions. The process of impregnation offilter matrix (20, 40) can occur under aseptic conditions in one of avariety of ways enumerated below:

-   -   1) absorbing the medication into the filter matrix in liquid        form followed by the removal of the liquid by evaporation within        72 hours;    -   2) pulverizing the powdered or crystallized form of the        medication into the filter matrix;    -   3) freeze drying the medication into the filter matrix; or    -   4) stabilizing the volume of medication within an inert viscous        carrier/semi-permeable barrier as depicted in the filter matrix        in FIG. 7.

As depicted in 1, 2, 3, 3A, 4, and 5, once the medicated FMA (10, 32,62) is prepared under sterile conditions, it can be then individuallyaseptically packaged and sealed in a sterilized sleeve as depicted inFIG. 7 which can be made of paper, plastic or another suitable material.This medicated filter matrix applicator system of the present inventionin FIGS. 1, 3, and 5 facilitates instilling ophthalmic agents in varioushead positions and body posture, virtually independent of gravity. FIG.9 illustrates the administration of an ocular compound to the eye usingthe present invention FMA (10) depicted in FIG. 1.

Operational Method

In use, the medicated filter matrix applicator is removed from thesterilized sleeve (FIG. 7) and a drop of sterile saline is placed uponthe filter matrix. In the case of FIG. 5, the medicated FMA is simplyremoved from the protective sleeve and is ready for application withoutactivation from sterile saline. The lower lid of the eye is then pulleddown to expose the conjunctiva of the eye and the FMA is directlyapplied thereto (FIG. 9). The pharmaceutically active solution then isreleased from the FMA to the eye via capillary action (which describeshow a liquid can move against the forces of gravity), the forces ofcovalent bonding, and Van der Waal forces which determine the attractionof particles in a solution at different temperatures). This method ofdrug delivery would allow for the entrapment and effective release ofmedication for easy instillation of a dose of medicine to an eye nearlyindependent of gravity, less dependent on dexterity, with reducedspillage and overflow, and the possibility of fewer or no preservatives.

In the case of FIG. 5, the semi-permeable component of the FMA (65) isslowly dissolved after being released from the inert viscous carrier.Furthermore, direct corneal and conjunctival absorption is able to beoptimized because of reduced reflex tearing, drop spillage, and dropsplash back, as is the case in all FMA embodiments (10, 32, 62, 70,100). Alternatively, a dry medicated FMA (10, 32, 62) can be held in thelower fornix to enable the natural and reflex tears to extract themedication from the filter matrix.

This method of ophthalmic agent delivery is easy to use, safe, sanitary,comfortable, and effective. It greatly reduces the physical andpsychological difficulties associated with eye drop instillation viastandard eye dropper bottles and tubes. The medicated FMA has a vastrange of applications ranging from personal use for eye medicineinstillation for patients, to instillation of ocular agents bycaregivers in a private or institutional setting, to the application ofdiagnostic ocular agents for practitioners, even to the instillation ofocular agents and pharmaceuticals in a veterinary setting. Patient,caregiver, and health care practitioner preference will result insignificantly improved compliance and reduced side effects.

Experiments

Referring to FIG. 10-13, there are shown several experiments conductedby the applicant to show the ease of use and efficacy of the device.Referring to FIG. 10, there is shown an experiment measuring the levelof dilation using hydroxyamphetamine/tropicamide. In this experiment,the filter matrix applicator (FMA) was impregnated with approximately ⅓of a drop of hydroxyamphetamine/tropicamide. Then the FMA was air-driedat room temperature over a 72 hour period. To activate the FMA, a dropof saline solution was applied to the FMA and the FMA was subsequentlyapplied to the left eye. Measurements were observed under normal roomlighting. As depicted, it was noted that upon application of thehydroxyamphetamine/tropicamide—FMA (hFMA) to the left eye while leavingthe right eye as an untreated control, the subject experienced asubstantial and effectively sustained dilation in the left eye. The hFMAwas easily self-applied in less than 2 seconds using a mirror. There wasno report of burning upon instillation (as is usually noted withstandard hydroxyamphetamine/tropicamide eye dropper bottleinstillation). However, gradual onset of low grade burning was notedwithin 1 minute of application (although significantly less and ofshorter duration than with hydroxyamphetamine/tropicamide in eye dropform from an eye dropper bottle). The subject was a 35 year old male.

Referring to FIG. 11, there is shown the results of the experimentmeasuring the amplitude of accommodation usinghydroxyamphetamine/tropicamide. The method of impregnation of the filtermatrix applicator (FMA) was via solution absorption followed byair-drying at room temperature over a 3 day period. The FMA was thenactivated with the application of a drop of saline solution and then theFMA was subsequently applied to the left eye. The subject was a 35 yearold male. It was noted that upon application of thehydroxyamphetamine/tropicamide—FMA (hFMA) to the left eye while leavingthe right eye as an untreated control, that the subject experienced a35% reduction in accommodative ability. Again, the subject reported noburning upon installation, which is usually noted with standardhydroxyamphetamine/tropicamide eye dropper bottle installation. However,gradual onset of low grade burning was noted within 1 minute ofapplication using the FMA, but the burning was significantly less and ofshorter duration than with hydroxyamphetamine/tropicamide using aconventional eye dropper bottle.

Referring to FIG. 12, there is shown the results of the experiment usingtimolol. The method of impregnation of the filter matrix applicator(tFMA) was via solution absorption followed by air-drying at roomtemperature for a 24 hour period. The timolol—FMA (tFMA) was thenactivated with the application of saline solution and subsequentlyapplied to the right eye. One eye drop of timolol from an eye dropperbottle was instilled in the left eye. The results were subsequentlymonitored and compared.

The FMA was easily self-applied by the patient in less than 2 secondsusing a mirror. The subject reported no burning upon installation norwas there ocular irritation. In addition, no conjuctival or cornealstaining was noted in the right eye. However, the subject reportedsignificant and sustained irritation (grade 5 out of 10) of the lefteye. In addition, there was mild corneal staining noted along withsubsequent nasal conjunctival staining with grade 1 hyperemia upon eyedrop instillation from the eye dropper bottle. The corneal staining andhyperemia persisted over a 24 hour period (in the left eye), while therecontinued to be no complaint about the right eye. Subject refusedfurther testing from the eye dropper bottle of timolol due to thediscomfort. A sizable reduction in intraocular pressure (IOP) was notedusing both methods (nearly 30% reduction in the right eye and 35%reduction in the left eye). It should be noted that due to theimpregnation technique, the tFMA contained approximately ⅓ of the volumeof 1 standard eye drop (therefore it is assumed that the tFMA containedonly ⅓ of the active ingredient of timolol, yet still attained a robustIOP reduction). This demonstrates similar efficacy at a significantlylower dose—which is closer to the minimum effective dose (MED) requiredto achieve the targeted IOP reduction (lowering the amount of active andinactive ingredients and preservatives to achieve the desired effect).The subject was a 65 year old male.

Referring FIG. 13, there is shown the results of the experiment usingolopatadine. The method of impregnation of the filter matrix applicator(FMA) was via solution absorption followed by air-drying at roomtemperature for a 24 hour period. The olopatadine—FMA (oFMA) was thenactivated with the application of saline solution and subsequentlyapplied to the left eye. It was noted that upon application of oFMA tothe left eye while leaving the right eye as an untreated control, thatthe subject experienced a substantial and sustained comfort over a 24hour period in the left eye. The FMA was applied easily in less than 2seconds using a mirror (as the oFMA was self-applied). There was noreport of burning upon instillation nor was ocular irritation noted. Inaddition, no conjunctival or corneal staining was noted in the left eye.The right eye remained untreated for the duration of day 1. On day 2,one olopatadine eye drop from a bottle was instilled in the right eyedue to the subject's request to relieve allergic conjunctivitissymptoms—after which, relief was quickly achieved at a rate similar tothat of oFMA. Although no subsequent conjunctival redness, staining, norcorneal staining was noted for the right eye, significant difficultywith instillation was observed. It took the subject several attemptsbefore 1 drop was successful instilled into the subject's right eye.

In conclusion, the foregoing experiments show that the method of thepresent invention provides an easy, safe, sanitary, comfortable, andeffective delivery of ocular pharmaceuticals to the eye. It greatlyreduces the physical and psychological difficulties associated with eyedrop instillation via standard eye drop bottles and tubes. As statedbefore, the medicated FMA and un-medicated FMA have a vast range ofapplications ranging from primary uses for eye medicine instillation forthe individual patient, to installation of eye medication by a caregiverin a private or institutional setting, to the application andinstillation of diagnostic eye pharmaceuticals and agents by healthcarepractitioners, even to the instillation of ophthalmic mediations toveterinary patients. Patient, caregiver, and healthcare practionerpreference will result in improved compliance and reduced side effects.Previous systems have been mainly paper fiber based. In addition, theywere mainly used for the delivery of dyes into the eye for diagnosticpurposes. If they were impregnated with medication, the amount ofmedication precipitated out into a drop was variable due to loss throughthe fibered strip over a period of time of saturation. The medicated FMAaddresses this issue with the addition of a variable/adjustableabsorptive filter matrix and a semi-permeable to impermeable waterproofmembrane. This allows the filter matrix to hold the medication in agiven area until it is precipitated out to the eye by applying awater-based solution (saline) over that same given area. Thus the FMAwould then deliver a consistent and precise dose to the eye. The abilityto have increased accuracy of dose and drug concentration decreaseswasteful drop application and increases drug efficacy. This method canbe easily adapted to replace most eye dropper bottle systems.

REFERENCES

-   (1) S Dinslage, M Diestellhorst, A Weichselbaum, R Swerkrup. British    Journal of Ophthalmology 2002; 86 1114-1117 doi 10.11362    BJ0.86.10.114-   (2) Abdul-Fattah A M, Bhargawa H N, Korb D R, Glonek T, Finnemore V    M, Greiner J V, Optom Vis Sci 2002 July; 79(7): 435-8-   (3), (4), (7) A Lux, S Maier, S Dinslage, R Suverkrup, M    Deistelhorst, British Journal of Ophthalmology 2003; 87 436-440 doi    10.11436/bjo.87.4.436-   (5), (6) Basics of Ocular Drug Delivery Systems. International    Journal of Research in Pharmaceutical and Biomedical Sciences. ISSN:    2229-3701

What is claimed is:
 1. A hand-held ophthalmic applicator device fordelivery of a precise dose of an ocular agent fluid to the conjunctivaof an eye, the hand-held ophthalmic applicator device comprising: ahandle configured to be held by a human hand; a filter matrix elementinseparably attached to the handle, the filter matrix element being madeof a plurality of interwoven fibers of material and having dimensions tocontain the precise dose of ocular agent fluid; and a waterproof barriermembrane securely attached between the handle and the filter matrixelement, wherein when a solution is applied to the filter matrixelement, the barrier membrane prevents the solution from flowing fromthe filter matrix element into the handle and contains within the filtermatrix element the precise dose of the ocular agent fluid to be placedto the conjunctiva of the eye.
 2. The hand-held ophthalmic applicatordevice of claim 1, wherein the filter matrix element is impregnatedbetween the plurality of interwoven fibers with a medicated dose of anocular agent that is pulverized in a granular form.
 3. The hand-heldophthalmic applicator device of claim 1, wherein the waterproof barriermembrane is made of an impermeable material.
 4. The hand-held ophthalmicapplicator device of claim 1, wherein the waterproof barrier membrane ismade of a semi-permeable material.
 5. The hand-held ophthalmicapplicator device of claim 1, wherein: the handle has a width at anattachment point of the waterproof barrier membrane to the handle; andthe waterproof barrier membrane extends the width of the handle at theattachment point.
 6. The hand-held ophthalmic applicator device of claim1, wherein the plurality of fibers of the filter matrix element is madeof an absorbent material.
 7. The hand-held ophthalmic applicator deviceof claim 1, wherein the plurality of fibers of the filter matrix elementis made of a non-absorbent material.
 8. The hand-held ophthalmicapplicator device of claim 1, wherein the plurality of fibers of thefilter matrix element includes a blend of materials selected to providethe precise dose of the ocular fluid agent to the conjunctiva.
 9. Thehand-held ophthalmic applicator device of claim 1, wherein: the handleis elongate and includes a first end and an opposing second end; and thebarrier membrane extends from the first end to the second end of thehandle.
 10. The hand-held ophthalmic applicator device of claim 1,wherein the handle has a length of approximately 2 inches and a width ofapproximately 0.25 inch.
 11. The hand-held ophthalmic applicator deviceof claim 1, and further comprising the precise dose of the ocular agentfluid disposed within the filter matrix element.
 12. The hand-heldophthalmic applicator device of claim 1, and further comprising aprecise dose of a non-fluid ocular agent within the filter matrixelement that, in combination with the solution, forms the ocular agentfluid.
 14. The hand-held ophthalmic applicator device of claim 1,wherein the filter matrix element has a shape from the group consistingof cylindrical, polygonal, circular, oval, and elliptical.
 15. Thehand-held ophthalmic applicator device of claim 1, wherein the elongatedhandle is made of paper or plastic.
 16. The hand-held ophthalmicapplicator device of claim 1, wherein the filter matrix is being made ofa material from the group consisting of cotton, rayon, silk, nylon, andplastic fiber.
 17. A method of applying a precise dose of an ocularagent fluid to a conjunctiva of an eye, the method comprising: holding,by a human hand, a hand-held ophthalmic applicator device including ahandle, a filter matrix element, inseparably attached to the handle,that is made of a plurality of interwoven fibers of material and thathas dimensions to contain the precise dose of ocular agent fluid, awaterproof barrier membrane securely attached between the handle and thefilter matrix element, and the precise dose of the ocular agent fluidentrapped within the filter matrix element; and pulling a lower eyelidof the eye downward to expose the conjunctiva of the eye; and placingthe filter matrix element in contact with the conjunctiva of the eyesuch that the ocular agent fluid is transferred from the hand-heldophthalmic applicator device to the conjunctive of the eye.
 18. Themethod of claim 17, and further comprising: applying a solution to thefilter matrix element to form, with a non-fluid ocular agent within thefilter matrix element, the precise dose of the ocular agent fluid.
 19. Amethod of making a hand-held ophthalmic applicator device for deliveryof a precise dose of an ocular agent fluid to the conjunctiva of an eye,the method comprising: forming a handle configured to be held by a humanhand; inseparably attaching to the handle a filter matrix element madeof a plurality of interwoven fibers of material and having dimensions tocontain the precise dose of ocular agent fluid; and securely attaching awaterproof barrier membrane between the handle and the filter matrixelement, wherein when a solution is applied to the filter matrixelement, the barrier membrane prevents the solution from flowing fromthe filter matrix element into the handle and contains within the filtermatrix element the precise dose of the ocular agent fluid to be placedto the conjunctiva of the eye.
 20. The method of claim 19, and furthercomprising applying the solution to the filter matrix element.
 21. Themethod of claim 19, and further comprising: impregnating the filtermatrix element between the plurality of interwoven fibers with a precisedose of an ocular agent in a granular form.
 22. The method of claim 19,and further comprising: applying the ocular agent fluid to the filtermatrix element; and thereafter, drying the ocular agent fluid therein.23. The method of claim 22, wherein the drying comprises freeze drying.24. The method of claim 22, wherein the drying comprises air drying.